Endothelin-1 induced contraction of rat aorta in Ca2(+)-free medium independent of phosphatidylinositol 4,5-bisphosphate (PIP2) breakdown.
1. The mechanism of endothelin-1 (ET)-induced contraction of rat aorta in Ca2(+)-free medium was investigated and compared with that of phenylephrine-induced contraction, measuring tension development and inositol 1,4,5-trisphosphate (IP3) formation. 2. After Ca2(+)-deprivation for 10 min, ET (10 nM) induced only a slow sustained contraction, whereas phenylephrine (10 microM) evoked a rapid phasic contraction followed by a small sustained one. Prolonged incubation of the strips in Ca2(+)-free medium (for 100 min) abolished the phasic contraction evoked by phenylephrine, but had no effect on the sustained contraction by either stimulant. 3. ET (100 nM) and phenylephrine (10 microM) stimulated inositol trisphosphate formation and these effects were inhibited by TPA (5 microM). 4. TPA (5 microM) had no effect on ET (10 nM)-induced contraction in Ca2(+)-free medium, but inhibited the contraction by phenylephrine (10 microM). 5. The ET- and phenylephrine-induced contractions in Ca2(+)-free PSS were inhibited by H-7, a protein kinase C inhibitor. 6. The difference and similarity of signal transduction pathways between alpha 1-adrenoceptor and ET receptor systems were discussed.
Huang
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Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Takanayagi
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Hisayama
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D000818:Animals; D001013:Aorta, Thoracic; D002118:Calcium / Q000378:metabolism; D003470:Culture Media; D016232:Endothelins / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D003470:Culture Media; D016232:Endothelins; D010656:Phenylephrine; D015544:Inositol 1,4,5-Trisphosphate; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium